- News from Lincoln University –
Most people with Batten disease won’t live past the age of 30. Ella Harris is using a special flock of sheep to help understand why.
Ella is a PhD student at Lincoln University. She originally studied a Bachelor of Food Science on a LU Sports Scholarship. Now she’s contributing to the field of biochemistry and working to improve the lives of children with a life-limiting disease.
Batten disease is an extremely rare neurodegenerative disorder affecting 1 child out of every 100,000 born. Early symptoms present in the same way as other less harmful developmental problems, making it very difficult to diagnose.
“One of the first things they often experience is vision loss. But a child who is starting to lose their vision may not be able to communicate that clearly. Because Batten disease affects neurodevelopment, it also impacts their motor function and their ability to think and communicate.
“Maybe they’re just starting school, or they’re still at home and a parent notices they’re struggling. These parents are told to take their children to ophthalmologists. Maybe the child gets glasses, but that’s not going to help, and as they get older it gets worse.”
Severity varies between the subtypes of Batten disease, but most people with it won’t survive past early adulthood.
Researchers are still trying to understand how Batten disease disrupts cells, making it very difficult to develop effective treatments. Ella’s background in biochemistry gives her a unique perspective on this problem. She wants to understand what’s going wrong inside cells and identify what future therapies could target.
The cells within our body carry out an extraordinary number of chemical reactions every second. Almost all these reactions create waste byproducts — essentially cellular gunk. To keep cells functioning properly, most contain a tiny recycling centre called the lysosome, which breaks down that waste material and keeps your cells squeaky clean.
Research has shown us that the lysosomes in people with Batten disease don’t work efficiently enough, which results in a build-up of waste material within their cells.
“Lysosomal waste just accumulates more and more, so you can see how it would relate to their symptoms getting worse over time.”
But that observation invites a classic case of correlation verses causation. There’s still debate whether the buildup is the cause of the problem or simply a symptom.
That brings us to a very special flock of Lincoln University sheep.
Humans aren’t the only species affected by Batten disease. It’s been found in dogs, monkeys and other animals. Ella’s research uses sheep.
Lincoln University has a flock of about 200 sheep which are kept specifically for Batten disease research. The flock is divided into two groups, each carrying a different genetic form of the disease. A careful breeding programme allows Lincoln to maintain these sheep and study how the disease progresses.
The sheep are kept in good conditions and monitored closely. When the severity of their symptoms begins to significantly affect their quality of life, they are humanely euthanised and their tissues are used for research.
For her research, Ella studies tissue collected from the sheep’s brain as well as its peripheral organs like the heart, liver and pancreas. There are many uses for the tissue, but one of Ella’s goals is isolate the accumulated cellular waste and determining what it’s made of. This can offer insights into which parts of the cellular process are malfunctioning.
After processing the tissue, Ella separates the cellular components using a centrifuge. Tissue from a sheep with Batten disease produces a visible layer of lysosomal material at the bottom of the test tube. It’s dark in colour and very obvious to the naked eye. No comparable accumulation occurs in tissue is from a healthy sheep.
Ella then extracts lipid (fats) from this material and creates a detailed profile showing exactly what the waste material is made of.
What she’s found is a that a large proportion of this accumulated material is made up of mitochondrial components — material from the energy-producing structures inside cells.
Her findings build upon an old discovery pioneered by a now retired Lincoln University researcher Professor David Palmer decades ago. Technology has developed since then and now Ella wants to take this idea a step further.
“There’re very few people still asking, ‘why is this here?’
“More than 50% of the waste material is made up of this particular protein, and no one knows why.”
Ella’s passion for biochemistry began during her Bachelor of Food Science, where she became fascinated by the molecular processes that keep cells functioning. That interest led her to a Master of Biochemistry before moving straight to a PhD.
That love for biochemistry and the chance to help people is what brought Ella here. She’s using her experience in biochemistry to help figure out the next step towards solving the problem.
“If we can find out what is happening within the cells of these animals, then we can better understand what is happening in children as well.
“There’s overlap with other neurodegenerative diseases like Alzheimer’s, and what we learn could help us understand those conditions too.
“We know there is a connection between mitochondria and Batten disease. Now it’s about figuring out which questions to ask and how we can analyse them to conclusively determine the cause.”
Ella first became interested in Batten disease after a lecture during her Master of Biochemistry. She wrote an essay on the topic, which became the groundwork for her PhD thesis.
“I’ve always loved being a problem solver, I love connecting the dots and discovering the mechanisms of everything. It’s almost a little bit like being a detective. A biochemical detective.
“These are people that don’t get a lot of attention because it’s such a rare disorder. Everybody wants to cure the common cold, because imagine how many millions of dollars in pharmaceuticals you could sell that for.
“Without people like us, these families and these children could be left behind. The last thing I want is for them to feel alone.
“I could solve crimes, but if I can use my skillset to do something that helps these families, then why wouldn’t I?”
Ella’s research is one example of how curiosity-driven science can have a real impact for families affected by rare diseases.
Source: Lincoln University
